The specific aims of this proposal are to characterize two recently identified forms of pepsinogen I (PG I) that have been designated Big-Big PG I and Big PG I based on their higher molecular weights than the third form of PG I, now designated Little PG I, and to complete studies on serum pepsinogen II (PG II) levels. Big-Big PG I and Big PG I will be isolated and purified from human gastric mucosa by sequential gel exclusion chromatography, immunoadsorption, and ion exchange chromatography. Antibodies to these antigens will be raised in rabbits and, if necessary, made monospecific by immunoadsorption. The antibodies will be used to purify additional antigen and to develop specific radioimmunoassays for Big-Big PG I and Big PG I. The sequence of mucosal synthesis of the three forms of PG I, and their several electrophoretic constituents, will be determined in vitro by pulse-chase incubations of gastric mucosal biopsies followed by gel exclusion chromatography, polyacrylamide gel electrophoresis, and fluorography. The concentrations of Big-Big PG I, Big PG I, and PG II will be determined by radioimmunoassay in serum form control subjects and patients with disorders of the stomach and duodenum. The goals of this project are to determine the role of the pepsinogens in the pathogenesis of focal and diffuse disorders of the stomach and duodenum.